Neuro degenerative Flashcards
Neurodegenerative Diseases we discussed in class
◦ Alzheimer’s disease
◦ Parkinson’s disease
◦ Amyotrophic lateral sclerosis
◦ Pick’s disease
What is Alzheimer’s disease
is a degenerative brain disorder that develops in mid-to-late adulthood. It results in a progressive and irreversible decline in memory and a deterioration of various other cognitive abilities
What is the main pathology of Alzheimer disease?
cortical parts of the frontal and temporal regions of the brain degenerate
What are the histological changes with Alzheimer’s?
– Most prominent in the cortex
– Neuritic (senile) plaques
– Neurofibrillary tangles
– Degeneration with vacuoles and granules predominant
– Deposition of amyloid in the neuritic plaques and the wall of the cerebral vessels
What are the nonmodifiable risk factors of alzheimers
◦ Family history
◦ Genetics: Apo E2 gene may confer risk in some but it is not absolute
What are neurofibrillary “tangle” of Alzheimer’s disease? and composed of what?
Composed of cytoskeletal intermediate filaments that are toxic to brain tissues
What are the two classes of drugs approved to treat alzheimers?
cholinesterase inhibitors
N-methyl-d-aspartate (NMDA) receptor antagonist
What are the MOA of Cholinesterase drugs?
They block the breakdown of acetylcholine at the nerve synapse, making it more available for activating post-synaptic muscarinic receptors
What is the pathogenesis of Pick’s disease?
abnormal accumulation of tau protein in swollen neurons
It affects… everything
What is Lewy body disease?
Presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons.
Which parts of the brain do Lewy Bodies affect?
Cerebral Cortex
Limbic Cortex
Hippocampus
Midbrain and basal ganglia
Brain stem
(All parts of the brain)
Which population is of higher risk of Lewy body disease
Men
What is the first and second most common forms of dementia?
Alzheimers
Lewy Body dementia
What is parkinsons disease features?
Loss of neurons and pigmentation
Response to which pharmacological agent helps confirm diagnosis of Parkinson’s disease?
Levodopa
What is Levodopa?
Pro drug that makes up for loss of dopamine and it reduces bradykinesia symptoms
What four categories of drugs can we use for slowing the progression of parkinsons?
1) Blocking peripheral metabolism of levodopa:
2) Blocking breakdown of dopamine at the neuron:
3) Reducing reuptake of dopamine:
4) Direct dopamine agonists:
What is aducanumab
Targets beta amyloid plaques and reduce the cognitive decline of alzheimers
What is the pathogenesis of Pick’s disease?
Tau protein (Pick bodies) accumulation
What type of drugs are people with LB disease sensitive to?
antipsychotic drugs
What does aggregated AB do?
damage neurons and can increase oxidative stress inflammation and mitochondrial dysfunction
What does the cerebral cortex do?
Controls many functions including processing perception though and language
What does the limbic cortex do?
Plays a mjaor role in emotions and behavior
What does the hippocampus do/
Memories
What does the midrbain and basal ganglia do?
Movement
What does hte brain stem do?
Alertness
What is cholinergic hypothesis with regards to dementia
The decrease in acetylcholine
What is the amyloid hypothesis?
Accumulation of B-amyloid and disrupts communication of neurons
What is the Tau hypothesis?
The dissociation of the neurotubule Tau proteins
What are Cholinesterase inhibitors?
These stop the breakdown Ach
What are the cholinesterase inhibitors? (3)
DRG
Donepezil
Rivastigmine (More inhibition)
Galantamine
What are the NMDA receptor antagonists MOA?
Memantine blocks excessive Ca intake into the neurons and it slows it down
What do AchEis do?
slow down the breakdown of acetyl choline
What does carbidopa do?
decreases systemic metabolism for levodopa to reach the brain
What is the MOA of lecanumab?
Targets amyloid beta in the brain
What is a goal of parkinsons treatment?
Increase dopamine
What is the direct dopamine agonists?
bromocriptine
What is a inhibitor of dopamine?
amandatine
What does selegiline do?
block breakdown of dopamine
